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Inspired by the close interplay between cellular physiological states and immunoregulatory functions, we propose ASCENT, a nanovaccine platform integrating nanovesicles derived from activated platelets and senescent tumor cells to naturally co\u2010present antigens and co\u2010stimulatory molecules, thereby enabling dual\u2010pathway T cell activation. Specifically, senescent tumor cells promote antigen presentation via upregulated major histocompatibility\u00a0complex\u2010I (MHC\u2010I) molecules, whereas activated platelets increase the surface expression of CD40L and OX40L, thereby enhancing immune activation. Thus, without genetic or chemical engineering, ASCENT can effectively stimulate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells through both antigen self\u2010presentation and dendritic cell\u2010mediated antigen presentation, ultimately eliciting robust immune responses. This non\u2010engineered, physiologically modulated nanovaccine exhibits broad\u2010spectrum antitumor activity while simultaneously inducing durable systemic immune memory to effectively suppress tumor recurrence and metastasis. Overall, the ASCENT nanovaccine provides new perspectives on rational vaccine design, emphasizing the importance of engaging both direct and indirect T cell activation in reinforcing cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.73231","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:12:51Z","timestamp":1777630371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Non\u2010Engineered Physiologically Modulated Nanovesicles Augment Antitumor Immune Responses via Dual\u2010Pathway T Cell Activation"],"prefix":"10.1002","volume":"38","author":[{"given":"Xiaoyuan","family":"Fan","sequence":"first","affiliation":[{"name":"School of Pharmacy Shenyang Pharmaceutical University Shenyang China"},{"name":"Department of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Shenyang 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